Uterine leiomyomas (fibroids) are the leading indication for hysterectomy in the United States. Despite the morbidity and high medical costs associated with fibroids, there has been little epidemiologic study of this condition in the United States. Even prevalence data have been lacking. Uterine leiomyomas are histologically identifiable as benign smooth muscle tumors with varying amounts of associated fibrous tissue. Many women have more than one uterine leiomyoma, but apparently each is clonally distinct. Chromosomal aberrations have been identified in 25-50% of specimens studied, and several specific cytogenetic changes are quite common. The causes of uterine fibroids are unknown. These benign tumors are hormone-dependent. They develop after puberty and regress after menopause. The hypogonadal environment associated with gonadotropin-releasing-hormone-analogue treatment results in tumor regression, as does treatment with the antiprogestin RU486. Both estrogen and progesterone are considered important stimulants, or at least permissive factors for tumor growth. The few epidemiologic studies that have been conducted suggest that pregnancy and possibly smoking and exercise are protective, while age (up to menopause) and long interval of menstrual cycling after last pregnancy are associated with increased risk. Other possible risk factors are early age of menarche, radiation exposure, and obesity. Most previous work has focused on patients who required surgery. The risk factors found in such studies could, therefore, arise because the factor influenced symptom development or was associated with the willingness to have surgery rather than fibroid initiation and growth. Previously identified risk factors need to be studied further, and other potential risk factors, such as breastfeeding and amenorrhea need to be considered. Even the most consistently found association, that between age and risk of fibroids, needs further study to understand why the association occurs. Are older women at higher risk simply because more time for cell transformation has passed, or might the perimenopausal hormonal milieu be a stimulant for growth? This paucity of information provided the impetus for designing an epidemiologic study of uterine fibroids. The NIEHS Uterine Fibroid Study was designed to address three specific aims: 1) To estimate the age-specific cumulative incidence of leiomyomas in black and white women, aged 35-49. 2) To identify risk factors for the condition. 3) To compare proliferation, apoptosis, hormone receptors, growth factors, and other growth-mediating factors in tumor and matching myometrial tissues collected at time of hysterectomy. Premenopausal participants are being followed to identify new cases of fibroids and document changes in fibroids and symptoms for those previously diagnosed. Work completed during FY02: 80% of premenopausal participants in the NIEHS Uterine Fibroid Study completed a followup interview to assess change in fibroid status, symptoms, and treatment. We estimated the cumulative incidence of fibroids by age 50 for African American and whites. Over 80% of African Americans develop the tumor and nearly 70% of whites. As reported in the literature, we found that pregnancy is protective for fibroids. We hypothesize that the protective mechanism is linked to the remodelling of uterine tissue following parturition, with elimination of small fibroids at that time. Preliminary data from the NIEHS Uterine Fibroid Study support this hypothesis, and we have initiated a study of pregnant women to look for changes in fibroids after pregnancy. Measuring pthalates. Phthalate monoesters have a biologic half-life of approximately 12 hr, and little is known about the temporal variability and daily reproducibility of urinary measures in humans. To explore these aspects, we measured seven phthalate monoesters and creatinine concentration in two consecutive first-moming urine specimens from 46 African-American women, ages 35-49 years, residing in the Washington, DC, area in 1996-1997. We measured phthalate monoesters using high-pressure liquid chromatography followed by tandem mass spectrometry on a triple quadrupole instrument using atmospheric pressure chemical ionization. We detected four phthalate monoesters in all subjects, with median levels of 31 ng/mL for monobenzyl phthalate (mBzP), 53 ng/mL for monobutyl phthalate (mBP), 211 ng/mL for monoethyl phthalate (mEP), and 7.3 ng/mL for monoethylhexyl phthalate (mEHP). These were similar to concentrations reported for other populations using spot urine specimens. Phthalate levels did not differ between the two sampling days. The Pearson correlation coefficient between the concentrations on the 2 days was 0.8 for mBP, 0.7 for mEHP, 0.6 for mEP, and 0.5 for mBzP. These results suggest that even with the short half-lives of phthalates, women's patterns of exposure may be sufficiently stable to assign an exposure level based on a single first morning void urine measurement. Fibroid Growth Study (Barbara Davis, PI). Enrollment has begun in the NIEHS/NCMHD Fibroid Growth Study (http://www.niehs.nih.gov/fibroids/study.htm). The purpose of this study is to learn more about why some fibroids grow to become problems for women while others do not. It is hoped that the findings from this study will help us develop strategies to prevent fibroids in women at high risk for problems, or develop new therapies that reduce the need for radical surgical procedures like hysterectomy.